Protection Of Chlorpromazine On PC-12 Cell Oxygen-glucose Deprived And The Mechanisms Mediated The Effects

Objective:To observe Chlorpromazine-type drugs for the protection of oxygen-glucose deprivation-induced cell injury and its mechanism. Set up oxygen-glucose nerve cells model of nerve injury in vitro by PC-12 cell line.Method:1, With sodium dithionite at the same time build a medium-glucose in vitro model of oxygen-glucose deprivation. Experiment is divided into CON,MOD, CPZ1 and CPZ2.2, Chlorpromazine with MTT to determine the role of non-toxic to cells, the concentration of the drug, chlorpromazine observation of oxygen-glucose deprivation-induced cell injury.3, RT-PCR was used to detected changes of cell survival-related gene NF-κB, caspase-3, Bax, Bcl-2, Clc-2, Clc-3, Beclin, AT1, and ACE on the mRNA level and semi-quantitative Analysis.4,Western blotting was used to analyze the expression of p65,p50 in each group.Results:1, Compared with the control group, model group, the cell survival rate dropped significantly; Compared with model group, low-dose group and high dose group of cells significantly increased the survival rate. 2, Compared with the control group, model group of the mRNA level of IκB was significantly increased; Compared with model group, low-dose group and high dose group of the mRNA levels of IκB decreased.3, Compared with the control group, model group of the IκB level of caspase-3 significantly increased; Compared with model group, low-dose group and high dose group of the caspase-3 significantly reduced the level of mRNA.4,I Compared with the control group, model group P65/P50 significantly reduced the protein level; Compared with model group, low-dose group and high-dose group P65/P50 significantly increased the protein level.5, Compared with the control group, model group, low-dose group and high dose group of the Bax / Bcl-2, Clc-2, Clc-3, AT1, ACE, Beclin 1 mRNA level did not change significantly.Discussion:In order to explore the ischemic injury of the nerve cells in the pathogenesis and treatment of hypoxic-ischemic disease gene targeted therapy to provide a theoretical basis, we make use of in vitro rat neural cell line of pheochromocytoma PC-12 cells at the nerve cells in vitro glucose of the hypoxic model; and explore the chlorpromazine on oxygen-glucose deprivation caused cell injury in rats. Experimental results show that chlorpromazine on the oxygen-glucose deprivation-induced cell injury has significant protective effect, the protective mechanism is probably reduced the NF-κB inhibitor IκB expression, an increase of nuclear transcription factor NF-κB expression and reduce wither The expression of apoptosis-related genes or chlorpromazine are probably exert a direct inhibitory role in apoptosis, the specific mechanisms still need to be further explored.Conclusion:1, Successful construction of oxygen-glucose deprivation in vitro model of cell injury PC-12 .Chlorpromazine has obvious protective effect.2, Chlorpromazine on the oxygen-glucose deprivation-induced PC-12 cell protective mechanism of injury are possible by increasing the expression of NF-κB and IκB inhibition so as to promote the entry of NF-κB nuclear to play a role in promoting cell proliferation.3, Chlorpromazine can reduce apoptosis, which may reduce the activation of NF-κB may also be relevant because chlorpromazine may exert a direct inhibitory role of apoptosis.4, Other apoptosis and proliferation-related signaling pathway-related genes and chlorpromazine protection mechanisms there is no significant relationship between.